Research will be continued on the isolation of somatomedin from human plasma. Starting with acid ethanol extracts, the techniques to be used are gel chromatography, isoelectric focusing, ion exchange chromatography, and polyacrylamide gel electrophoresis. The fractions will be analyzed by competitive radioreceptor assays for somatomedin and for insulin-like activity. This will be complemented by assays in rat cartilage and chick fibroblast cell cultures. The mechanism of somatomedin production will be studied by perfusing isolated rat liver with growth hormone and other substances in enriched media. Biological studies will be undertaken both in vivo and in vitro to define the physiologic role of somatomedin. Competitive binding assay will be used to measure somatomedin levels in plasma under a variety of clinical circumstances.